Among the vaccine adjuvants evaluated in human trials, the emulsion-type adjuvants have the advantages of ease of manufacture and low costs. Freund's adjuvants and MONTANIDE® ISA 51 (ISA51), containing mineral oil and lipophilic emulsifier named mannide monooleate, are defined as water-in-oil (W/O) emulsions with dispersed antigenic media and continuous oily phases. Although the mechanisms of adjuvant's action are poorly understood, the W/O types of adjuvant products have been evaluated to improve the innocuity of the vaccine and to achieve long-term, protective immune responses. It is difficult to give injections with syringe needle having a small diameter. There are also local reactions at the injection site, which limit their applications to humans. To improve the injectability of such vaccines, a method for re-dispersing them in an aqueous phase containing a hydrophilic emulsifier TWEEN® 80 (polyoxyethylene sorbitan monooleate) has been described. Nevertheless, TWEEN® 80 is a lipid dispersant, can attack cell walls and hence is potentially toxic. Preclinical experience has found that TWEEN® 80-stabilized emulsions were generally more immunogenic than non-adjuvanted vaccines but also increased the reactogenicity.
To increase the number of safe emulsifiers for vaccine adjuvants, synthetic polymer is regarded as an interesting alternative to low-molecular weight surfactants (LMWS) because the size and the relative positions of hydrophilic and lipophilic blocks can be easily tailored by the order of the monomer addition and by the amounts of monomer used to produce a broad range of surfactant characteristics. One of the examples is TITERMAX®, in which a squalene-based water-in-oil (W/O) emulsion is stabilized by microparticulate silica and the non-ionic block copolymer polyoxyethylene-polyoxypropylene-polyoxyethylene (POE-POP-POE, known as PLURONIC® or POLOXAMER®). TITERMAX® elicits more potent immune responses than the LMWS-emulsified formulation but its application in human vaccine delivery is still dubious because the stabilizers used are toxic and non-biodegradable.
A heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies, especially in connection with enhancement of the water affinity of W/O emulsion-adjuvanted vaccines.